Efforts Continue to Refine Use of Checkpoint Inhibitors in NSCLC

Nivolumab (Opdivo) and pembrolizumab (Keytruda) have demonstrated significant promise in second-line non–small cell lung cancer (NSCLC), but questions remain on how either agent, as well as other immunotherapies on the horizon, will perform in the frontline.

The available evidence is mixed. Regarding pembrolizumab, the FDA granted a priority review to a supplemental biologics license application as a first-line treatment for patients with PD-L1–positive NSCLC, based on findings from the phase III KEYNOTE-024 trial. Here, pembrolizumab improved progression-free and overall survival (OS) versus chemotherapy in patients whose PD-L1 expression levels were >50%.

However, an announcement on the CheckMate-026 trial, which explored nivolumab as a frontline therapy for NSCLC patients with PD-L1 expression >5%, did not demonstrate an improvement in progression-free survival. Full results from either study have not yet been presented.

An even bigger question is how to determine which patients are fit to receive these immunotherapies—either as monotherapy or in combination. Such combination regimens do have the potential to elicit activity in patients with little to no PD-L1 expression, explained Hossein Borghaei, DO.

“We’re trying to figure out how to best select patients who would benefit from these agents without necessarily excluding everyone,” said Borghaei. “However, we are realizing that no single drug is necessarily appropriate in all patients. If we can limit the toxicities of these agents in patients who are not going to have a clinical benefit, that is a win-win for everybody.”

Borghaei, an associate professor at Fox Chase Cancer Center, highlighted checkpoint inhibitors in NSCLC during the 2016 OncLive State of the Science Summit on Advanced Non–Small Cell Lung Cancer, which took place on September 17 in Philadelphia. In an interview with OncLive, he provided additional insight on checkpoint inhibitors, determining patient selection, and how these therapies will continue to significantly impact the treatment landscape in NSCLC for years to come.

OncLive: What were some of the highlights from, your presentation on immunotherapy in NSCLC?

Borghaei: I discussed the recently published studies with a couple of different agents in this category. One was with nivolumab, and I presented 2 separate phase III studies—one in patients with squamous cell carcinoma and one with the nonsquamous cell carcinoma of the lung. Both phase III studies were conducted in patients in the second-line setting. The results of both of these studies, as published previously, showed that treatment with immunotherapy, in this case nivolumab, was superior to treatment with standard docetaxel in this particular patient population.

I discussed our available data regarding the use of PD-L1 as a marker for selection of patients who could potentially benefit from these treatments and some of the controversies around that.

I then presented data on the use of pembrolizumab, another anti–PD-1 agent, that began based on a phase III randomized trial, and [was compared] against docetaxel in a very similar patient population. Again, the use of pembrolizumab was superior to docetaxel in terms of OS. Both of these agents have shown a favorable toxicity profile when compared with docetaxel—making these agents, potentially, a standard of care now for patients in this category.

Another presentation concentrated on use of another agent, atezolizumab (Tecentriq), which is a PD-L1 inhibitor as opposed to the PD-1 inhibitors pembrolizumab and nivolumab. Again, this study was very nicely done and was randomized head-to-head against docetaxel, which has been our standard chemotherapy. It showed that the use of a PD-L1 inhibitor was also superior compared to docetaxel.

Again, the key point here is that from a clinical efficacy point of view, all of these drugs are showing very good activity. Also, toxicity seems to be better with these drugs as opposed to the standard chemotherapy that we’ve been using for quite some time, so this is making these drugs an attractive alternative to standard chemotherapy—at least in a second- or third-line setting.

We know that studies have been conducted in the frontline setting, again, in select patient populations with high levels of expression. However, we don’t have all of the data regarding the clinical efficacy of these agents, so we’re waiting to see what happens when you use these agents in the frontline setting.